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HIV-1 detection in the olfactory mucosa of HIV-1-infected participants

Bertero, Lucaa,*; Joseph, Sarah Bethb,*; Trunfio, Mattiac; Allice, Tizianod; Catera, Sebastianoe; Imperiale, Danielef; Cassoni, Paolaa; Kincer, Laura Pescib; Pirriatore, Veronicac; Ghisetti, Valeriad; Amasio, Enricae; Zanusso, Gianluigig; Bonora, Stefanoc; Di Perri, Giovannic; Calcagno, Andreac

doi: 10.1097/QAD.0000000000002102

Objective: HIV infection chronically affects the central nervous system (CNS). Olfactory mucosa is a unique site in the respiratory tract that is directly connected to the CNS; thus we wanted to evaluate olfactory mucosa as a surrogate of CNS sampling.

Design: We conducted a preliminary study examining HIV populations and susceptible cells in the olfactory mucosa.

Methods: Olfactory mucosa was sampled by minimally invasive brushing. Cerebrospinal fluid (CSF) analyses were performed as per routine clinical procedures. Olfactory marker protein, CD4+, CD8+, and trans-activator of transcription (TAT) expressions were assessed by immunohistochemistry. Plasma, CSF, and olfactory mucosa HIV-RNA were quantified using the Cobas AmpliPrep/Cobas TaqMan assay, whereas HIV proviral DNA was evaluated on peripheral blood mononuclear cell and olfactory mucosa. HIV-1 env deep sequencing was performed for phylogenetic analysis.

Results: Among ART-naive participants, 88.2% (15/17), and among ART-treated participants, 21.4% (6/28) had detectable HIV-RNA in samples from their olfactory mucosa; CSF escape was more common in patients with olfactory mucosa escape (50 vs. 7.9%; P = 0.010). Olfactory mucosa samples contained few cells positive for CD4+, CD8+, or HIV-DNA, and no HIV TAT-positive cells, indicating that this approach efficiently samples virions in the olfactory mucosa, but not HIV-infected cells. Yet, using a deep sequencing approach to phylogenetically compare partial HIV env genes in five untreated participants, we identified distinct viral lineages in the OM.

Conclusions: The results of this study suggest that nasal brushing is a well tolerated and useful technique for sampling the olfactory mucosa. HIV-RNA was detected in most naïve and in some treated patients, warranting larger longitudinal studies.

aUnit of Pathology, Department of Medical Sciences, University of Torino, Torino, Italy

bDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

cUnit of Infectious Diseases, Department of Medical Sciences, University of Torino

dLaboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia

eUnit of Otorhinolaryngology, Ospedale Maria Vittoria

fUnit of Neurology, Ospedale Maria Vittoria, ASL ‘Città di Torino’, Torino

gDepartment of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.

Correspondence to Luca Bertero, MD, Pathology Unit, Department of Medical Sciences, University of Torino, Via Santena 7, 10126 Torino, Italy. E-mail:

Received 24 August, 2018

Accepted 26 October, 2018

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